This invention relates to novel aliphatic acids containing isoprenoid 1,5-diene structural units and to a method for preparing them. More particularly this invention relates to the preparation of such acids by the selective gamma-alkylation of a dicopper(I) dienolate of an aliphatic .alpha.,.beta.-unsaturated acid with an allylic electrophile.
The alkylation of aliphatic .alpha.,.beta.-unsaturated carbonyl compounds at the gamma position would appear to be a convenient route for the synthesis of compounds containing isoprenoid 1,5-diene units which compounds are important in many biological systems and natural products. This approach is severely limited, however, because all reported alkylations occur largely at the alpha carbon atom ("Molecular Rearrangements", P. de Mayo, Ed., Interscience, New York, New York, 1963, p. 345). For example, in the case of an .alpha.,.beta.-unsaturated ester, it has been shown that the lithium enolate formed by treatment of ethyl trans-3-methyl-2-hexenoate with lithium diisopropylamide in tetrahydrofuran undergoes alkylation with allyl bromide predominately at the alpha position and produces the isomeric alpha- and gamma-alkylation products in a 95:5 ratio. ##STR1## More desirable results were obtained with the copper enolate, which was found to give a 44:56 ratio of alpha to gamma products (J. A. Katzenellenbogen et al., J. Amer. Chem. Soc., 96, 5662(1974)).
Other investigators have reported the alkylation of the lithium enolate of ethyl crotonate with methyl iodide yielded less than 5% of the gamma isomer (J. L. Herrman et al., Tetrahedron Lett., 2433(1973)). Somewhat better gamma-regioselectivity was obtained, 60:40 alpha- to gamma-alkylation, when crotonic acid was alkylated with methyl iodide (P. E. Pfeffer et al., Tetrahedron Lett., 1163(1973)).
A method for selective gamma-alkylation of .alpha.,.beta.-unsaturated carbonyl compounds in the synthesis of compounds containing isoprenoid 1,5-diene units is highly desirable because alkylation at the gamma site preserves both the structure of the carbon skeleton (isoprene polymer) and the pattern of oxygen functionality (at chain termini) as they are found most often in natural products. Such a structural and functional pattern can be advantageously employed in the synthesis of insect pheremones, insect juvenile hormones, and components of perfumes.